Effects of Methylphenidate (Ritalin®) on the Neural Basis of Anxiety

NCT02021214 | Completed Early Phase 1

• 1 other identifier: 131297
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

In the present study, investigator will investigate the effects of methylphenidate (40 mg) on mPFC activity in healthy male volunteers during fear extinction using functional magnetic resonance imaging (fMRI). Additionally, investigators will examine the effects of methylphenidate during aversive interoceptve arousal. The present study will help to identify brain structures and networks involved in anxiety and will give insights for methylphenidate as a possible adjunct to behavioral therapy for patients with anxiety disorders. Further, this study may provide important information about the possible use of fMRI to help the development of drugs for the treatment of anxiety disorders.

Conditions

PTSD

Keywords

Methylphenidate; Fear extinction; fMRI; mPFC

Outcome Measures

Primary Outcomes (1)

• Changes in blood oxygenation level-dependent BOLD signal responses

  Methylphenidate-induced changes in BOLD signal responses in brain regions relevant in fear disorders (e.g. amygdala, insula, and prefrontal cortex) during a fear extinction task compared to placebo.

  6 hours

Secondary Outcomes (3)

• Changes in BOLD signal responses

  6 hours

• Changes in skin conductance response

  6 hours

• Latency and accuracy during a interoceptive stimulus task

  2 hours

Study Arms (1)

Methylphenidate/Placebo

EXPERIMENTAL

40 mg Methylphenidate, per os, single dose Placebo, single dose

Drug: Methylphenidate; Drug: Placebo

Interventions

Methylphenidate DRUG

Also known as: Ritalin

Methylphenidate/Placebo

Placebo DRUG

Methylphenidate/Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male subjects, 18 to 40 years of age, inclusive.
• In good general health (as determined by medical history, blood pressure, and ECG), especially no findings (including concomitant medications) that would constitute contraindications for treatment with any of the study drugs.
• A weight of \> 120 lbs (55 kg) and a BMI between 18 to 30 kg/m2, inclusive.
• Participants must be willing to drink only alcohol-free liquids and no xanthine-containing liquids (such as coffee, black or green tea, red bull, chocolate) the day before and during the study day.
• Subjects able to participate and willing to give written informed consent and to comply with the study restrictions.

You may not qualify if:

• History of any hematological, hepatic, respiratory, cardiovascular (including structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease or myocardial infarction), renal or CNS disease (including seizures), gallbladder removal or other medical or surgical condition that could alter the absorption, metabolism or elimination of drugs.
• Family history of sudden death or ventricular arrhythmia.
• Any major illness (as judged by the study physician) within 1 month prior to first dose.
• Current or history of any psychiatric disorder, marked anxiety, tension and agitation.
• History of glaucoma.
• History (including family history) of motor tic or diagnosis of Tourette's syndrome.
• History of psychotropic medicine and/or alcohol dependence.
• Active suicidal ideation, history of suicidal behavior, or otherwise considered at high suicidal risk by trained study staff using the C-SSRS.
• Positive urine toxicology (drugs of abuse as determined by a positive urine test) at screening and before each drug administration.
• Use of any medications or herbal remedies, including psychotropic medicines and regular sleep medications, taken within 14 days or 6 times the elimination half-life of the medication (whichever is longer) prior to the first dose and throughout the study, with the exception of acetaminophen for minor pains, occasional use of sleeping medication as long as it is not taken the evening prior to a visit, medications explicitly approved by the investigator and the sponsor.
• Past intolerance (including allergic) to any of the study medications or components thereof.
• Supine systolic blood pressure (BP) \>140 or \>90 mmHg, diastolic BP \<90 mmHg or \<50 mmHg (mean of two measurements at screening) and current or past history of clinically significant hypertension.
• Current smoker (\> 10 cigarettes/day); habitual caffeine consumption of more than 400 mg/d (approximately 4 cups of coffee or equivalent).
• QTcF \> 450 msec based on the average interval on triplicate ECGs. Notable resting bradycardia (mean HR \< 45 bpm) or notable resting tachycardia (mean HR \> 90 bpm).
• Contraindication to magnetic resonance imaging.

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (1)

UCSD Psychiatry Clinical Research

San Diego, California, 92037, United States

Location

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Methylphenidate

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Martin P Paulus, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: DOUBLE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blind, cross-over design with two drug conditions. Drug conditions are placebo and methylphenidate 40 mg. Order will be balanced and pseudo-random.

Study Record Dates

• First Submitted: December 9, 2013
• First Posted: December 27, 2013
• Study Start: March 1, 2014
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: February 28, 2020

Record last verified: 2020-02

Locations

US (1)